On 2014 Mar 04, David Keller commented:

The quantum treatment discontinuity at 190 mg/dL lacks biological plausibility

The case of the 57-year-old white man in Table 2 illustrates a peculiar aspect of the new lipid treatment guidelines: his recommended treatment is high-intensity statin therapy if his LDL is greater than or equal to 190 mg/dL, but if his LDL is below 190 mg/dL, then no treatment is recommended. It seems odd that an LDL of 189 mg/dL is not considered high enough to warrant any statin therapy at all, but if his LDL is 1 point higher, it triggers the need for maximum-dose statin therapy. The true variation of cardiovascular risk with LDL seems unlikely to exhibit this sort of quantum jump discontinuity. Cardiovascular risk seems more likely to be a smooth, continuous and monotonically increasing function of LDL, and amelioration of this risk would therefore justify a range of statin doses, starting with low dose statins to treat mild LDL elevations, medium dose statins to treat moderate LDL elevations, and high dose statins to treat severely elevated LDL levels of 190 mg/dL or higher. This is how clinicians have historically treated patients for hyperlipidemia. If the data does not exist to support this range of treatments, it may be because mild and moderate LDL elevations do not cause enough adverse events fast enough to generate statistically significant results over the course of a clinical trial for this category of patient. Guideline-issuing organizations should revisit evidence-based guidelines which include recommendations that lack biological plausibility. Since biological variables are generally continuous, while data points from major clinical trials are discrete, interpolation and curve-fitting should be permissible in evidence-based guidelines, in order to avoid the kind of quantum discontinuity encountered in this case.

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On 2014 Feb 23, David Keller commented:

None

On 2014 Feb 23, David Keller commented:

None

On 2014 Feb 18, David Keller commented:

Error in Table 2, Case Examples: "White man with high cholesterol"

In Table 2 of this review of the 2013 ACC-AHA cholesterol treatment guidelines, statin therapy was not recommended for a 57-year-old white man with total cholesterol (TC) of 255 mg/dL, HDL cholesterol of 45 mg/dL, no triglyceride (TG) or LDL levels specified, and no other coronary risk factors or contraindications to statin therapy specified. The new guidelines recommend high-intensity statin therapy for this man if his LDL cholesterol level is at least 190 mg/dL, which is entirely possible. The Friedewald equation, valid for TG levels under 200 mg/dL, states that TC = HDL + LDL + TG/5 (1). By plugging his HDL and total cholesterol levels into the Friedewald equation, we find that if his triglyceride level is 100 mg/dL or less, his LDL cholesterol would be 190 mg/dL or higher. The new guidelines recommend high-intensity statin therapy for primary prevention in patients whose LDL is at least 190 mg/dL, barring contraindications which this patient is not said to have. Since it cannot be determined whether his LDL is higher or lower than the 190 mg/dL threshold for treatment, we cannot determine whether he requires statin therapy with the information given. This case illustrates that the new evidence-based guidelines emphasize the paramount role of LDL cholesterol levels in treatment decisions, and that statins are the treatment of choice for preventing cardiovascular events. Table 2 presents only HDL and total cholesterol levels for each patient, which was formerly sufficient information when treatment decisions were based on the TC/HDL ratio, but not under the new guidelines.

1. Fukuyama N et al. Validation of the Friedewald Equation for Evaluation of Plasma LDL-Cholesterol. J Clin Biochem Nutr. 2008 July; 43(1): 1–5.

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On 2014 Feb 18, David Keller commented:

Error in Table 2, Case Examples: "White man with high cholesterol"

In Table 2 of this review of the 2013 ACC-AHA cholesterol treatment guidelines, statin therapy was not recommended for a 57-year-old white man with total cholesterol (TC) of 255 mg/dL, HDL cholesterol of 45 mg/dL, no triglyceride (TG) or LDL levels specified, and no other coronary risk factors or contraindications to statin therapy specified. The new guidelines recommend high-intensity statin therapy for this man if his LDL cholesterol level is at least 190 mg/dL, which is entirely possible. The Friedewald equation, valid for TG levels under 200 mg/dL, states that TC = HDL + LDL + TG/5 (1). By plugging his HDL and total cholesterol levels into the Friedewald equation, we find that if his triglyceride level is 100 mg/dL or less, his LDL cholesterol would be 190 mg/dL or higher. The new guidelines recommend high-intensity statin therapy for primary prevention in patients whose LDL is at least 190 mg/dL, barring contraindications which this patient is not said to have. Since it cannot be determined whether his LDL is higher or lower than the 190 mg/dL threshold for treatment, we cannot determine whether he requires statin therapy with the information given. This case illustrates that the new evidence-based guidelines emphasize the paramount role of LDL cholesterol levels in treatment decisions, and that statins are the treatment of choice for preventing cardiovascular events. Table 2 presents only HDL and total cholesterol levels for each patient, which was formerly sufficient information when treatment decisions were based on the TC/HDL ratio, but not under the new guidelines.

1. Fukuyama N et al. Validation of the Friedewald Equation for Evaluation of Plasma LDL-Cholesterol. J Clin Biochem Nutr. 2008 July; 43(1): 1–5.

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